FR Organische Chemie, Universität des Saarlandes, D 66041 Saarbrücken, Germany.
Chem Commun (Camb). 2019 Mar 19;55(24):3433-3444. doi: 10.1039/c9cc00573k.
It is shown that the performance of allosteric systems regarding the efficiency and the speed of response depends critically on the strain energy of the equilibrating conformers and of the corresponding interconversion transition state. The affinity of a substrate A can be large enough to overcome in the absence of an effector E by induced fit the strain involved in the formation of an optimal conformation for binding A. The efficiency as given by the ratio KAE/KA of binding constants in the presence or absence of an effector is, for many published synthetic allosteric systems, relatively low; in practice this means that these only function within rather limited concentration ranges. A small KAE/KA ratio means that the binding strength of A or the corresponding signal will increase only little by adding an effector, and may need higher concentration of E. Implementation of steric distortion in the minor conformer can lead to reduced binding of A in the absence of the effector E. Destabilization of conformers can also result from the inclusion of high energy water molecules within a cavity. Furthermore, until now it has been overlooked that strain in the transition state can lead to reaction times of up to days, and thus to the neglect of experimental observation. The role of conformational changes within an allosteric molecule is characterized with a variety of calixarenes and other compound classes, offering a clue for the design of more efficient synthetic systems with high cooperativity.
研究表明，变构系统的效率和响应速度取决于平衡构象的应变能以及相应的互变过渡态。在没有效应物 E 的情况下，如果底物 A 的亲和力足够大，它可以通过诱导契合克服形成与 A 结合的最佳构象所涉及的应变。在存在或不存在效应物的情况下，结合常数 KAE/KA 的效率相对较低；实际上，这意味着这些系统仅在相当有限的浓度范围内起作用。较小的 KAE/KA 比值意味着添加效应物后 A 的结合强度或相应信号的增加幅度很小，可能需要更高浓度的 E。在次要构象中实现空间变形可能导致在没有效应物 E 的情况下 A 的结合减少。构象的不稳定性也可能是由于腔内包含高能水分子所致。此外，到目前为止，人们还忽略了过渡态中的应变可能导致反应时间长达数天，从而忽略了实验观察。各种杯芳烃和其他化合物类别的变构分子内构象变化的作用特点为设计具有高协同性的更有效合成系统提供了线索。
